Faculty Profile

Rachel Hazan, Ph.D.

Areas of Research: My laboratory is currently investigating the molecular basis for breast cancer metastasis by studying the cooperation between N-cadherin and the FGFR leading to epithelial to mesenchymal transition and cancer cell survival.

Professional Interests

Cell-cell adhesion is a primary modulator of morphogenetic events during normal embryonic development. Metastatic dissemination of epithelial tumor cells is also strongly influenced by the activity of cell-cell adhesion molecules, in particular members of the cadherin family. My laboratory has shown that N-cadherin, a cadherin involved in dynamic processes such as cell migration and neurite outgrowth, is upregulated in invasive breast cancer cells and promotes metastasis of breast cancer cell lines. In contrast, E-cadherin, known to promote stable epithelial contacts, is lost during metastatic progression. Our data suggest that cadherin switching during tumor progression has a broader consequence than a simple change in cell-cell adhesion. The shift in cadherin expression also affects proteolytic activity of cells, their migration, invasiveness and metastasis. We and others have shown that even in the presence of E-cadherin, and strong cell-cell adhesiveness, N-cadherin can convert poorly invasive breast cancer cell lines into invasive and metastatic tumors, thus suggesting a dominant role for N-cadherin in this process. These effects of N-cadherin are mainly due to a functional cooperation with the FGF receptor resulting in epithelial to mesenchymal transition, cell signaling and morphological changes leading to metastasis. Thus our hypothesis is that N-cadherin upregulation in tumor cells is a key step in a series of interdependent molecular changes which lead to metastasis.

More recently, we discovered that Retinal cadherin (R-cadherin), a classic cadherin highly expressed in the brain and retina is also present in the mammary epithelium. We showed that similarly to E-cadherin, R-cadherin acts as an invasion suppressor gene which is downregulated in invasive duct carcinomas. Moreover, R-cadherin knockdown in mammary gland tissue leads to disruption of morphogenesis and gain of metastastic properties. Conversely, R-cadherin expression in aggressive tumor cells suppresses invasion and metastasis, and restores glandular morphogenesis.

My laboratory is currently investigating: 1) the molecular basis for cooperation between N-cadherin and the FGF receptor responsible for epithelial to mesenchymal transition (EMT) and metastasis with the goal of obtaining functional inhibitors of metastasis. 2) Regulation of EMT and metastasis by the MAPK and AKT signaling pathways 3) the relationship between cell cycle progression and tumor metastasis. 4) The mechanism of HER2 therapeutic resistance in breast cancer. 5) Cancer stem cells and their role in breast cancer metastasis.